Journal of Shandong Normal University(Natural Science), Volume. 40, Issue 2, 95(2025)

RESEARCH PROGRESS ON STEM CELLS AND HUMAN HEALTH

Pan Jie1 and Nakayama Akihiro2
Author Affiliations
  • 1School of Life Sciences, Shandong Normal University, 250358, Jinan, China
  • 2Peking University Health Science Center, 100191, Beijing, China
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    References(111)

    [1] [1] Becker A J,Mc C E,Till J E. Cytological demonstration of the clonal nature of spleen colonies derived from transplanted mouse marrow cells[J]. Nature,1963,197: 452-454.

    [2] [2] Thomson J A,Itskovitz-Eldor J,Shapiro S S,et al. Embryonic stem cell lines derived from human blastocysts [J]. Science,1998,282(5391):1145-1147.

    [3] [3] Richard A Y. Control of the embryonic stem cell state [J]. Cell,2011,144: 940-954.

    [5] [5] Sean J M,Allan C S. Stem cells and niches: mechanisms that promote stem cell maintenance throughout life [J]. Cell,2008,132: 598-611.

    [6] [6] Okuchi Y,Reeves J,Ng S S,et al. Wnt-modified materials mediate asymmetric stem cell division to direct human osteogenic tissue formation for bone repair[J]. Nature Material,2021,20: 108-118.

    [7] [7] Patricia A Zuk. The adipose-derived stem cell: looking back and looking ahead [J]. Molecular Biology of the Cell,2010,21: 1783-1787.

    [8] [8] Liguo Z,Suchart K,Yiyi Y,et al. Insulin negatively regulates dedifferentiation of mouse adipocytes in vitro [J]. Adipocyte,2020,9 (1):24-34.

    [9] [9] Jie P,Suchart K,Laihao L,et al. Autophagy participants in the dedifferentiation of mouse 3T3-L1 adipocytes triggered by hypofunction of insulin signaling [J]. Cellular Signalling,2021,80: 109911.

    [10] [10] Stuart H O,Leonard I Z. Hematopoiesis: an evolving paradigm for stem cell biology [J]. Cell,2008,132: 631-644.

    [11] [11] Poliwoda S,Noor N,Downs E,et al. Stem cells: a comprehensive review of origins and emerging clinical roles in medical practice [J]. Open Medical Publishing,2022,3(14):2035-8164.

    [12] [12] Wojciech Z,Maciej D,Maria S,et al. Stem cells: past,present,and future [J]. Stem Cell Research & Therapy,2019,10: 68.

    [13] [13] Guan J,Wang G,Wang J,et al. Chemical reprogramming of human somatic cells to pluripotent stem cells [J]. Nature,2022,605: 325-331.

    [14] [14] Hockemeyer D,Soldner F,Cook E G,et al. A drug-inducible system for direct reprogramming of human somatic cells to pluripotency [J]. Cell Stem Cell,2008,3(3): 346-353.

    [15] [15] Medet,Jumabay,Kristina,et al. Dedifferentiated fat cells: a cell source for regenerative medicine [J]. World Journal of Stem Cells,2015,7 (10): 1202-1214.

    [16] [16] Matsumoto T,Kano K,Kondo D,et al. Mature adipocyte-derived dedifferentiated fat cells exhibit multilineage potential [J]. Journal of Cellular Physiology,2008,215(3): 210-222.

    [17] [17] Smriti M. Do stem-cell transplants increase cancer risk? Long-lived recipients offer clues [J]. Nature,2024: 791.

    [18] [18] Masumi U O,Jacob H,Isaac J,et al. Characterization of clonal dynamics using duplex sequencing in donor-recipient pairs decades after hematopoietic cell transplantation [J]. Science Translational Medicine,2024,16 (770).

    [19] [19] Hofer H R,Tuan R S. Secreted trophic factors of mesenchymal stem cells support neurovascular and musculoskeletal therapies [J]. Stem Cell Research & Therapy,2016,7: 131.

    [20] [20] Behzadifard M,Aboutaleb N,Dolatshahi M,et al. Neuroprotective effects of conditioned medium of mesenchymal stem cells (MSC-CM) as a therapy for ischemic stroke recovery: a systematic review [J]. Neurochemical Research,2023,48,1280-1292.

    [21] [21] Smith A G. Embryo-derived stem cells: of mice and men [J]. Annual Review of Cell and Developmental Biology,2001,17: 435-462.

    [22] [22] Chen W,Huang Q,Ma S,Li M. Progress in dopaminergic cell replacement and regenerative strategies for Parkinson's disease [J]. ACS Chemical Neuroscience,2019,10(2): 839-851.

    [23] [23] Madeleine J S,Madison C B P,Michael C F,et al. Neural stem cell treatment for perinatal brain injur: a systematic review and meta-analysis of preclinical studies [J]. Stem Cells Translational Medicine,2021,10 (12): 1621-1636.

    [24] [24] Rui W,Yiping G,Liying Z,et al. Physical exercise promotes integration of grafted cells and function recovery in an acute stroke rat model [J].Stem Cell Reports,2022,17(2): 276-288.

    [25] [25] Titomanlio L,Kavelaars A,Dalous J,et al. Stem cell therapy for neonatal brain injury: perspectives and challenges [J]. Annals of Neurology,2011,70 (5):698-712.

    [26] [26] Xu P F,Borges R M,Fillatre J,et al. Construction of a mammalian embryo model from stem cells organized by a morphogen signalling centre[J]. Nature Communications,2021,12: 3277.

    [27] [27] Jesse V V,Adriano B,Helene K,et al. Mouse embryonic stem cells self-organize into trunk-like structures with neural tube and somites[J].Science,2020,370(6522): eaba4937.

    [28] [28] Aguilera-Castrejon A,Oldak B,Shani T,et al. Exutero mouse embryogenesis from pre-gastrulation to late organogenesis [J]. Nature,2021,593: 119-124.

    [29] [29] Poliwoda S,Noor N,Downs E,et al. Stem cells: a comprehensive review of origins and emerging clinical roles in medical practice [J].Orthopedic Reviews,2022,3(14):

    [30] [30] Wojciech Z,Maciej D,Maria S,et al. Stem cells: past,present,and future [J]. Stem Cell Research & Therapy,2019,10: 68.

    [31] [31] Esparza A,Jimenez N,Borrego E A,et al. Review: Human stem cell-based 3D in vitro angiogenesis models for preclinical drug screening applications[J]. Molecular Biology Reports,2024,51: 260.

    [32] [32] Amadei G,Handford C,Qiu C,et al. Embryo model compeletes gastrulation to neurulation and organogenesis[J]. Nature,22,610: 143-153.

    [33] [33] Bailey A T W,Carlos W G,Riza M D,et al. Transgene directed induction of a stem cell-derived human embryo model [J]. Nature,2023,06,15. 545082.

    [34] [34] Bernardo O,Emilie W,Vladyslav B,et al. Transgene-free ex utero derivation of a human post-implantatione embryo model solely from genetically unmodified na ve PSCs [J]. Nature,2023,06,14. 544922.

    [36] [36] Bernadette A C,Connor J L,Mary J S,et al. Hematopoietic stem cells preferentially traffic misfolded proteins to aggresomes and depend on aggrephagy to maintain protein homeostasis [J]. Cell Stem Cell,2023,30(4): 460-472.

    [37] [37] Takebe T,Sekine K,Enomura M,et al. Vascularized and functional human liver from an iPSC-derived organ bud transplant [J]. Nature,2013,499: 481-484.

    [38] [38] Sekine K,Ogawa S,Tsuzuki S,et al. Generation of human induced pluripotent stem cell-derived liver buds with chemically defined and animal origin-free media [J]. Scientific Reports,2020,10: 17937.

    [39] [39] Koike H,Iwasawa K,Ouchi R,et al. Modelling human hepato-biliary-pancreatic organogenesis from the foregut-midgut boundary[J]. Nature,2019,574(7776).

    [40] [40] Kasey Y C L,Hernan R,Carlos W G,et al. Mouse embryo model derived exclusively from embryonic stem cells undergoes neurulation and heart development[J]. Cell Stem Cell,2022,29(10): 1445-1458.

    [41] [41] Gianluca A,Charlotte E H,Chengxiang Q,et al. Synthetic embryos complete gastrulation to neurulation and organogenesis [J]. Nature,2022,610,143-153.

    [42] [42] Rodriguez F A,Wolock S,Weinreb C,et al. Clonal analysis of lineage fate in native haematopoiesis [J]. Nature,2018,553: 212-216.

    [43] [43] Balboa D,Barsby T,Lithovius V,et al. Functional,metabolic and transcriptional maturation of human pancreatic islets derived from stem cells[J]. Nature Biotechnology,2022,40: 1042-1055.

    [44] [44] Chang H G,Dibyendu C,Cristiano P V,et al. Specific mesoderm subset derived from human pluripotent stem cells ameliorates microvascular pathology in type 2 diabetic mice [J]. Science Advances,2022,8 (9).

    [45] [45] Murase Y,Yokogawa R,Yabuta Y,et al. In vitro reconstitution of epigenetic reprogramming in the human germ line [J]. Nature,2024,631: 170-178.

    [46] [46] Okubo T,Rivron N,Kabata M,et al. Hypoblast from human pluripotent stem cells regulates epiblast development [J]. Nature,2024,626: 357-366.

    [47] [47] Tan T,Wu J,Si C,et al. Chimeric contribution of human extended pluripotent stem cells to monkey embryos ex vivo [J]. Cell,2021,184(8): 2020-2032.

    [48] [48] Shi L,Huang H,Lu X,et al. Effect of human umbilical cord-derived mesenchymal stem cells on lung damage in severe COVID-19 patients: a randomized,double-blind,placebo-controlled phase 2 trial [J]. Signal Transduction and Targeted Therapy,2021,6(3):9.

    [49] [49] Guan J,Wang G,Wang J,et al. Chemical reprogramming of human somatic cells to pluripotent stem cells [J]. Nature,2022,605: 325-331.

    [50] [50] Mazid M.,Ward C,Luo Z,et al. Rolling back human pluripotent stem cells to an eight-cell embryo-like stage [J]. Nature,2022,605: 315-324.

    [51] [51] Li J,Zhu Q,Cao J,et al. Cynomolgus monkey embryo model captures gastrulation and early pregnency [J]. Cell Stem Cell,2023,30(4): 362-377.

    [52] [52] Liu W X,Tan S J,Wang Y F,et al. Melatonin promotes the proliferation of primordial germ cell-like cells derived from porcine skin-derived stem cells: a mechanistic analysis [J]. Journal of Pineal Research,2022,73: e12833.

    [53] [53] Zhang S,Chen S,Li Y,et al. Melatonin as a promising agent of regulating stem cell biology and its application in disease therapy [J].Pharmacological Research,2017,117: 252-260.

    [55] [55] Cheng H,Shang D,Zhou R. Germline stem cells in human [J]. Signal Transduction and Targeted Therapy,2022,7: 345.

    [56] [56] Gentile L,Cebria F,Bartscherer K. The planarian flatworm: anin vivomodel for stem cell biology and nervous system regeneration [J]. Disease Models & Mechanisms,2011,4: 12-19.

    [57] [57] Molina M D,Cebri F. Decoding stem cells: an overview on planarian stem cell heterogeneity and lineage progression [J]. Biomolecules,2021,11(10): 1532.

    [58] [58] Martyn I,Kanno T Y,Ruzo A,et al. Self-organization of a human organizer by combined Wnt and Nodal signalling [J]. Nature,2018,558:132-135.

    [59] [59] Chichagova V,Sanchez-Vera I,Armstrong L,et al. Generation of human induced pluripotent stem cells using RNA-based sendai virus system and pluripotency validation of the resulting cell population [J]. Methods in Molecular Biology,New York: Humana Press,NY,2015:1353.

    [60] [60] Christa B,Hsu-Hsin C,Jose M P,et al. A murine ESC-like state facilitates transgenesis and homologous recombination in human pluripotent stem cells [J]. Cell Stem Cell,2010,6: 535-546.

    [61] [61] Chou Y F,Chen H H,Eijpe M,et al. The growth factor environment defines distinct pluripotent ground states in novel blastocyst-derived stem cells [J]. Cell,2008,135: 449-461.

    [62] [62] Charles E. Murry,Gordon Keller. Differentiation of embryonic stem cells to clinically relevant populations: lessons from embryonic development[J]. Cell,2008,132: 661-680.

    [63] [63] Takahashi K,Tanabe K,Ohnuki M,et al. Inducetion of pluripotent stem cells from adult human fibroblasts by defined factors [J]. Cell,2007,131: 861-872

    [64] [64] Lee J T. Epigenetic regulation by long noncoding RNAs [J]. Science,2012,338(6113): 1435-1439.

    [65] [65] Chen T,Dent S Y. Chromatin modifiers and romodellers: regulators of cellular differentiation [J]. Nature Reviews Genetics,2014,15: 93-106.

    [66] [66] Jonathan H,Pratibha S,Tiffany A T,et al. Rapid mobilization reveals a highly engraftable hematopoietic stem cell [J]. Cell,2016,172(1): 191-204.

    [67] [67] Elaine F,Tudorita T,Geraldine G. Socializing with the neighbors stem cells and their niche [J]. Cell,2004,116: 769-778.

    [68] [68] Takahashi K,Yamanaka S. Inducetion of pluripotent stem cells from mouse embryonic and adult fibrotblast celtures by defined factors [J]. Cell,2006,126: 663-676.

    [69] [69] Rudolf J,Richard Y. Stem cells,the molecular circuitry of pluripotency and nuclear reprogramming [J]. Cell,2008,132: 567-582.

    [70] [70] Pellegrini S,Piemonti L,Sordi V. Pluripotent stem cell replacement approaches to treat type 1 diabetes [J]. Current Opinion in Pharmacology,2018,43: 20-26.

    [71] [71] Tabar V,Sarva H,Lozano A M,et al. Phase I trial of hES cell-derived dopaminergic neurons for Parkinson's disease [J]. Nature,2025,641: 978-983.

    [72] [72] Sawamoto N,Doi D,Nakanishi E,et al. Phase I/II trial of iPS-cell-derived dopaminergic cells for Parkinson's disease [J]. Nature,2025,641: 971-977.

    [73] [73] Gao C,Shi Q,Pan X,et al. Neuromuscular organoids model spinal neuromuscular pathologies in C9orf72 amyotrophic lateral sclerosis [J].Cell Reports,2024,43(3):113892.

    [74] [74] Bydon M.,Qu W,Moinuddin F M,et al. Intrathecal delivery of adipose-derived mesenchymal stem cells in traumatic spinal cord injury: phase I trial [J]. Nature Communications,2024,15: 2201

    [75] [75] Guo M,Pegoraro A F,Mao A,et al. Cell volume change through water efflux impacts cell stiffness and stem cell fate [J]. Proceedings of the National Academy of Sciences of the United States of America,2017,114(41): 201705179.

    [76] [76] Charles K F C,Gunsager S G,Rahul S,et al. Identification of the human skeletal stem cell [J]. Cell,2018,175(1): 43-56

    [77] [77] Xiao D,Liu X,Zhang M,et al. Direct reprogramming of fibroblasts into neural stem cells by single non-neural progenitor transcription factor Ptf1a [J]. Nature Communications,2018,9: 2865.

    [78] [78] Hu Y,Yang Y,Tan P,et al. Induction of mouse totipotent stem cells by a defined chemical cocktail [J]. Nature,2023,617: 792-797.

    [79] [79] Cote J A,Ostinelli G,Gauthier M F,et al. Focus on dedifferentiated adipocytes: characteristics,mechanisms,and possible applications [J].Cell Tissue Research,2019,378(3): 385-398.

    [80] [80] Ono H,Oki Y,Bono H,et al. Gene expression profiling in multipotent DFAT cells derived from mature adipocytes [J]. Biochemical and Biophysical Research Communications,2011,407(3): 562-567.

    [81] [81] Jumabay M,Abdmaulen R,Ly A,et al. Pluripotent stem cells derived from mouse and human white mature adipocytes [J]. Stem Cells Translational Medicine,2014,3(2): 161-171.

    [82] [82] Murata D,Yamasaki A,Matsuzaki S,et al. Characteristics and multipotency of equine dedifferentiated fat cells [J]. Journal of Equine Science,2016,27(2): 57-65.

    [83] [83] Kwok K H,Lam K S,Xu A. Heterogeneity of white adipose tissue: molecular basis and clinical implications [J]. Experimental & Molecular Medicine,2016,48(3).

    [84] [84] Louis F,Kitano S,Mano J F,et al. 3D collagen microfibers stimulate the functionality of preadipocytes and maintain the phenotype of mature adipocytes for long term cultures [J]. Acta Biomaterialia,2019,84: 194-207.

    [85] [85] Tathiane M M,Artem S,Andrew J G,et al. Machine learning identifies stemness features associated with oncogenic dedifferentiation [J]. Cell,2018,173: 338-354.

    [86] [86] Chen Z,Han F,Du Y,et al. Hypoxic microenvironment in cancer: molecular mechanisms and therapeutic interventions [J]. Signal Transduction and Targeted Therapy,2023 17,8(1):70.

    [87] [87] Bibhas R,Saradha V,Prasuna R,et al. Laterally confined growth of cells induces nuclear reprogramming in the absence of exogenous biochemical factors [J]. Proceedings of the National Academy of Sciences of the United States of America,2018,115(21): E4741-E4750.

    [88] [88] Shoshani O,Zipori D. Mammalian cell dedifferentiation as a possible outcome of stress [J]. Stem Cell Reviews Reports,2011,7(3): 488-493.

    [89] [89] Liao Y,Zeng Z,Ly F,et al. In vivo dedifferentiation of adult adipose cells [J]. PLoS One,2015,10(4).

    [90] [90] White M G,Shaw J A,Taylor R. Type 2 diabetes: the pathologic basis of reversible beta-cell dysfunction [J]. Diabetes Care,2016,39(11): 2080-2088.

    [91] [91] Kruglikov I L,Zhang Z,Scherer P E. The role of immature and mature adipocytes in hair cycling [J]. Trends in Endocrinology and Metabolism,2019,30(2): 93-105.

    [92] [92] Schffler A,Schlmerich J,Bchler C. Mechanisms of disease: adipocytokines and visceral adipose tissue-emerging role in intestinal and mesenteric diseases [J]. Nature Reviews Gastroenterology & Hepatology,2005,2: 103-111.

    [93] [93] Lei H,Hao H,Yihao Y,et al. Distinctive clinical and pathologic features of immature teratomas arising from induced pluripotent stem cell-derived beta cell injection in a diabetes patient [J]. Stem Cells and Development,2022,31: 5-6.

    [94] [94] Rohani L,Johnson A A,Naghsh P,et al. Concise review: molecular cytogenetics and quanlity control: clinical guanrdians for pluripotent stem cells [J]. Stem Cells Translational Medicine,2018,7: 867-875.

    [96] [96] Robert F,Julia R,Aina B M,et al. Design principles of cell-state-specific enhancers in hematopoiesis [J]. Cell,2025,188: 1-17.

    [97] [97] Taskiran II,Spanier K,Dickmanken H,et al. Cell-type-directed design of synthetic enhancers [J]. Nature,2024,626; 212-220.

    [98] [98] Jianling Z,Xinxing Z,Huanjing H,et al. Generation of human expandable limb-bud-like progenitors via chemically induced dedifferentiation[J]. Cell Stem Cell,2024,31(12); 1732 - 1740.e6].

    [99] [99] Xi F,Shentong M,Alejandro B,et al. A foundation model of transcription across human cell types [J]. Nature,2025,637(8047): 965-973.

    [100] [100] Du Y,Liang Z,Wang S,et al. Human pluripotent stem-cell-derived islets ameliorate diabetes in non-human primates [J]. Nature Medicine,2022,28,272-282.

    [101] [101] Li X H,Guo D,Chen L Q,et al. Low-intensity ultrasound ameliorates brain organoid integration and rescues microcephaly deficits [J]. Brain,2024,147: 3817-3833.

    [102] [102] Xiaochun Y,Daichao C,Qiushi S,et al. A live-cell image-based machine learning strategy for reducing variability in PSC differentiation systems[J]. Cell Discovery,2023,9 (1): 53.

    [103] [103] Yan L,Tu W,Zaho X,et al. Stem cell transplantation extends the reproductive life span of naturally aging cynomolgus monkeys [J]. Cell Discovery,2024,10: 111.

    [104] [104] Pan H,Guan D,Liu X,et al. SIRT6 safeguards human mesenchymal stem cells from oxidative stress by coactivating NRF2 [J]. Cell Research,2016,26: 190-205.

    [105] [105] Rasouli M,Naeimzadeh Y,Haschemi N,et al. Age-related alterations in mesenchymal stem cell function: understanding mechanisms and seeking opportunities to bypass the cellular againg [J]. Current Stem Cell Research & Therapy,2024,19(1): 15-32.

    [106] [106] Hade M D,Suire C N,Suo Z. Mesenchymal stem cell-derived exosomes: applications in regenerative medicine [J]. Cells,2021,10: 1959.

    [107] [107] Zhu Y,Huang C,Zheng L,et al. Safety and efficacy of umbilical cord tissue-derived mesenchymal stem cells in the treatment of patients with aging frailty: a phase I/II randomized,double-blind,placebo-controlled study [J]. Stem Cell Research & Therapy,2024,15: 122.

    [108] [108] Han Y,Li X,Zhang Y. Mesenchymal stem cells for regenerative medicine [J]. Cells,2019,8: 886.

    [109] [109] Yan P,Li Q,Wang L,et al. FOXO3-engineered human ESC-derived vascular cells promote vascular protection and regeneration [J]. Cell Stem Cell,2019,24(3): 447-461.

    [110] [110] Todd W D,Samuel F,et al. A longevity-specific bank of induced pluripotent stem cells from centenarians and their offspring [J]. Aging Cell,2024,24(1): e14351. https://doi.org/10.1111/acel.14351

    [111] [111] Lee L,James P,Zevon E S,et al. Optimism is associated with exceptional longevity in 2 epidemiologic cohorts of men and women [J].Proceedings of the National Academy of Sciences of the United States of America,2019,116: 18357-18362.

    [112] [112] Hashimoto K,Kouno T,Ikawa T,et al. Single-cell transcriptomics reveals expansion of cytotoxic CD4 T cells in supercentenarians [J].Proceedings of the National Academy of Sciences of the United States of America,2019,116(48): 24242-24251.

    [114] [114] Wilmanski T M,Diener C,Rappaport N,et al. Gut microbiome pattern reflects healthy ageing and predicts survival in humans[J]. Nature Metabolism,2021,3(2).

    [115] [115] Kikuch T,Morizane A,Doi D,et al. Human iPS cell-derived dopaminergic neurons function in a primate Parkinson's disease model [J].Nature,2017,548: 592-596.

    [116] [116] Wu C,Xu H H,Wu Z,et al. Subchondral injection of human umbilical cord mesenchymal stem cells ameliorates knee osteoarthritis by inhibiting osteoblast apoptosis and TGF-beta activity [J]. Stem Cell Research & Therapy,2025,16: 235.

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    Pan Jie, Nakayama Akihiro. RESEARCH PROGRESS ON STEM CELLS AND HUMAN HEALTH[J]. Journal of Shandong Normal University(Natural Science), 2025, 40(2): 95

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    Paper Information

    Received: Apr. 27, 2025

    Accepted: Aug. 22, 2025

    Published Online: Aug. 22, 2025

    The Author Email:

    DOI:10.3969/j.issn.1001-4748.2025.02.001

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